Hibiscus sabdariffa / Ca+2 Cancer Research Results

HibSad, Hibiscus sabdariffa: Click to Expand ⟱
Features:
Hibiscus sabdariffa (commonly known as Roselle)
It is rich in bioactive components such as polyphenols, anthocyanins, flavonoids, organic acids, and other antioxidants.
Hibiscus sabdariffa is rich in antioxidants and bioactive compounds that show potential anti-cancer effects by reducing oxidative stress, inhibiting cell proliferation, inducing apoptosis, and modulating inflammatory pathways.
Preparation / Fraction Main Constituents / Identity Main Cancer-Relevant Pathways ROS / Mitochondria Apoptosis / Cell Cycle Other Key Features
H. sabdariffa aqueous extract (HSE) Water-soluble mixed extract containing anthocyanins, phenolic acids, flavonoids, organic acids, polysaccharides and other hydrophilic constituents; composition varies strongly with plant part, extraction temperature and preparation. ↓ Akt/NF-κB signaling; ↓ proliferation; ↓ migration/invasion; modulation of ERα in some breast-cancer models; broad antioxidant and anti-inflammatory effects. Can ↑ ROS and ↓ mitochondrial membrane potential in susceptible cancer cells at cytotoxic concentrations, while showing antioxidant effects in normal or non-cancer systems. ↑ Bax/Bcl-2 ratio; ↑ caspase-mediated apoptosis; cell-cycle inhibition reported in several models. Closest experimental category to Hibiscus tea/decoctions, but many laboratory HSE preparations are more concentrated than dietary beverages. Mechanistically broad but poorly standardized.
H. sabdariffa polyphenol-rich extract (HPE) Concentrated polyphenolic fraction enriched in anthocyanins, flavonoids and phenolic acids, often prepared from calyces or leaves. ↑ p38 MAPK; ↑ p53 signaling; ↑ Fas/FasL; modulation of PI3K class III/Beclin-1/LC3; modulation of Akt/mTOR; ↓ invasive signaling. ↑ oxidative stress and mitochondrial dysfunction in cancer cells; mitochondrial signaling contributes to apoptosis. Strong ↑ apoptosis through intrinsic and extrinsic pathways; ↑ autophagy or autophagic cell death in selected models; ↓ proliferation. Generally produces stronger and more reproducible anticancer effects than crude aqueous extract because active polyphenols are enriched. Frequently used in gastric-cancer and melanoma mechanistic studies.
H. sabdariffa anthocyanins (HAs) Anthocyanin-rich fraction dominated by delphinidin-3-sambubioside and cyanidin-3-sambubioside, with related anthocyanins depending on cultivar and extraction. ↑ mitochondrial apoptotic signaling; modulation of MAPK pathways; ↓ proliferation; possible modulation of estrogen-dependent signaling in ER-positive cells. ↑ ROS in cancer cells at cytotoxic concentrations; ↓ mitochondrial membrane potential; anthocyanins can also act as antioxidants at lower concentrations or in non-cancer tissues. ↑ cytochrome-c release; ↑ caspase-3/-9; ↑ Bax/Bcl-2 ratio; ↑ apoptosis, particularly in leukemia and other sensitive cancer-cell models. More chemically defined than HSE or HPE. Systemic translation is limited by rapid metabolism and low circulating concentrations of intact anthocyanins after oral administration.
H. sabdariffa protocatechuic acid (PCA) Defined phenolic acid constituent and anthocyanin metabolite; chemically distinct single compound rather than an extract. ↓ RB phosphorylation; ↓ Bcl-2; modulation of p53-related stress pathways; inhibition of proliferation. Can promote oxidative stress and mitochondrial apoptotic signaling in cancer cells depending on dose and model; also has antioxidant activity in non-cancer systems. ↑ apoptosis; ↓ Bcl-2; ↑ hypophosphorylated RB; cell-cycle arrest/growth suppression. Particularly well characterized in HL-60 leukemia cells. Best suited to a separate database product if individual-compound mechanisms are being tracked. PCA is not specific to H. sabdariffa and occurs widely in foods and as a metabolite of several polyphenols.

Hibiscus sabdariffa — commonly known as roselle, is an edible medicinal plant whose calyces and leaves contain anthocyanins, polyphenols, flavonoids, phenolic acids, and organic acids. It is classified as a botanical food/nutraceutical and plant-extract modality rather than a defined anticancer drug. Standard abbreviations include HS and H. sabdariffa. The calyx is the predominant food and beverage source, whereas several anticancer studies have used leaf extracts, anthocyanin-rich fractions, or polyphenol-enriched preparations that are not compositionally equivalent to ordinary hibiscus tea. Important constituents include delphinidin-3-sambubioside, cyanidin-3-sambubioside, protocatechuic acid, and other polyphenols.

-Calyx — the thick, fleshy red structure surrounding the base of the flower and later the seed capsule. This is the main material used for hibiscus tea, beverages, extracts, and most commercial supplements. It is especially rich in anthocyanins, organic acids, and polyphenols.
-Epicalyx — a ring of smaller bract-like structures immediately outside the calyx. These are often harvested together with the calyx and may be included in dried commercial “hibiscus flower” material.

Primary mechanisms (ranked):

  1. Induction of intrinsic and extrinsic apoptosis through ↑ Bax/Bcl-2 ratio, mitochondrial dysfunction/cytochrome-c signaling, caspase activation, and p53/p38 MAPK/Fas/FasL pathways.
  2. Suppression of tumor-cell proliferation and survival through cell-cycle disruption and modulation of RB, p53, MAPK, Akt and related survival signaling.
  3. Mitochondrial oxidative stress with ↑ ROS and ↓ mitochondrial membrane potential in susceptible cancer cells; this contributes to apoptosis and can enhance chemotherapy-induced cytotoxicity.
  4. Autophagy modulation, including autophagic cell death in some melanoma models, with involvement of PI3K class III/Beclin-1/LC3 and Akt/mTOR signaling.
  5. Estrogen receptor α modulation in ER-positive breast cancer, including altered ERα localization/activity; this mechanism is subtype-dependent rather than a universal Hibiscus effect.
  6. Suppression of migration/invasion and other metastatic phenotypes in selected breast, prostate, and other tumor models.
  7. Anti-inflammatory and antioxidant modulation, including attenuation of pro-inflammatory and oxidative signaling; these effects are more established in non-cancer experimental and human contexts than as direct tumor-killing mechanisms.

Bioavailability / PK relevance: Hibiscus anthocyanins are orally absorbed but have low systemic bioavailability and are rapidly metabolized and eliminated. Human pharmacokinetic studies demonstrate circulating anthocyanin-derived compounds after oral Hibiscus extract, but exposure to intact parent anthocyanins is substantially lower than concentrations commonly used in mechanistic cell-culture studies. Extract composition, plant part, cultivar, processing, and extraction method materially affect exposure.

In-vitro vs systemic exposure relevance: Many anticancer experiments use approximately hundreds of µg/mL to mg/mL of crude or polyphenol-enriched extract, or high-µM to millimolar concentrations of individual phenolic compounds. These concentrations generally exceed plausible circulating concentrations following ordinary dietary Hibiscus consumption. Direct translation of in-vitro anticancer potency to oral tea or supplement use is therefore poor. Local gastrointestinal exposure may be considerably higher than systemic exposure.

Clinical evidence status: Cancer evidence is predominantly preclinical, consisting of cell-culture studies and limited animal models; there is no established human anticancer efficacy and no validated Hibiscus anticancer dosing regimen. Human RCT evidence is considerably stronger for blood-pressure reduction and some cardiometabolic effects than for cancer treatment. Hibiscus should therefore be categorized as preclinical for anticancer therapy, not as an established cancer adjunct. Oral Hibiscus preparations are generally well tolerated in short-term human studies, but clinically relevant hypotensive and glucose-lowering effects can occur, creating potential additive effects with antihypertensive or antidiabetic therapy.

Hibiscus sabdariffa Cancer-Relevant Mechanisms

Rank Pathway / Axis Cancer Cells Normal Cells TSF Primary Effect Notes / Interpretation
1 Mitochondrial and death-receptor apoptosis ↑ Bax; ↓ Bcl-2; ↑ cytochrome c; ↑ caspases; ↑ Fas/FasL ↔ or substantially less cytotoxicity (model-dependent) R/G ↑ Apoptosis Most consistently reproduced anticancer phenotype across gastric, leukemia, melanoma, prostate and breast models; both intrinsic mitochondrial and extrinsic death-receptor pathways are reported.
2 p53 and p38 MAPK stress signaling ↑ p53 phosphorylation; ↑ p38 MAPK; ↑ JNK (model-dependent) ↔ (context-dependent) R/G ↑ Stress-mediated apoptosis Particularly well characterized in gastric carcinoma; p38 MAPK/FasL signaling contributes directly to Hibiscus polyphenol-induced apoptosis.
3 Cell-cycle and RB survival control ↓ RB hyperphosphorylation; ↑ hypophosphorylated RB; ↓ proliferation ↔ (context-dependent) R/G Cell-cycle arrest and growth inhibition Protocatechuic acid from Hibiscus produced early RB modulation and Bcl-2 suppression in HL-60 leukemia cells; importance varies substantially with extract and tumor model.
4 Mitochondrial ROS and membrane potential ↑ ROS; ↓ mitochondrial membrane potential ↓ oxidative stress or ↔ (context-dependent) P/R Oxidative mitochondrial injury and apoptosis Hibiscus can act as a pro-oxidant selectively in stressed cancer cells despite its broader antioxidant reputation. Direction of ROS modulation is therefore cell-state and concentration dependent.
5 Chemosensitization ↑ response to taxol and cisplatin (model-dependent) Not established R/G ↑ Chemotherapy-induced apoptosis Reported primarily in breast-cancer cell models and associated with increased oxidative stress and mitochondrial depolarization. This remains preclinical and should not be interpreted as a validated clinical combination.
6 Autophagy and PI3K class III Beclin-1 LC3 ↑ autophagy; ↑ LC3-II; modulation of PI3K class III/Beclin-1 Not established R/G Autophagic cell death and apoptosis interaction Most clearly demonstrated with Hibiscus leaf polyphenolic extract in melanoma. Autophagy can be cytotoxic or protective depending on tumor context.
7 Akt mTOR survival signaling Modulated (model-dependent) ↔ (context-dependent) R/G Altered survival and autophagy signaling Linked particularly to Hibiscus-induced autophagy in melanoma. Evidence is less consistent than the apoptosis pathways and does not support a universal directional annotation across cancers.
8 Estrogen receptor alpha ↓ nuclear ERα activity/localization (context-dependent) Not established R/G Altered estrogen-dependent growth signaling Relevant primarily to ERα-positive breast cancer. Experimental enriched Hibiscus fractions alter ERα localization, while anthocyanins have also been investigated computationally as ERα ligands. The Nestronics ER↓ annotation is directionally plausible but currently supported there by only one paper.
9 Migration and invasion ↓ migration; ↓ invasion (model-dependent) Not established G ↓ Metastatic phenotype Observed in selected breast and other cancer models; mechanistic dependence varies with extract composition and tumor subtype.
10 Inflammatory and antioxidant signaling ↓ inflammatory signaling; ROS response ↔ or biphasic ↓ oxidative stress; ↓ inflammatory signaling R/G Reduced chronic oxidative and inflammatory stress Better supported as a systemic cardiometabolic and tissue-protective property than as a direct anticancer mechanism. Cancer cells can instead show acute ↑ ROS at cytotoxic concentrations.
11 Clinical Translation Constraint In-vitro cytotoxic concentrations frequently exceed systemic dietary exposure Human oral exposure generally tolerated at studied food/extract doses G Limits anticancer translation Low systemic bioavailability of intact anthocyanins, extensive metabolism, major extract standardization differences, absence of cancer RCTs, and reliance on high-concentration cell experiments are major limitations.

P: 0–30 min     R: 30 min–3 hr     G: >3 hr



Ca+2, Calcium Ion Ca+2: Click to Expand ⟱
Source:
Type:
In all eukaryotic cells, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+.
Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors.
In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2).
Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways.
Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer.
Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation.
High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses.
Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes.


Scientific Papers found: Click to Expand⟱
7361- HibSad,    Hibiscus sabdariffa L. - a phytochemical and pharmacological review
- Review, Var, NA
*Bacteria↓, *hepatoP↑, *diuretic↑, *LDL↓, *antiOx↑, *ACE/ACE1↓, *Ca+2↝, *toxicity↓, *ROS↓, *RenoP↑,

Showing Research Papers: 1 to 1 of 1

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 1

Pathway results for Effect on Cancer / Diseased Cells:


Total Targets: 0

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0)

ACE/ACE1↓, 1,   diuretic↑, 1,  

Redox & Oxidative Stress(tgid=1)

antiOx↑, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis(tgid=4)

LDL↓, 1,  

Migration(tgid=13)

Ca+2↝, 1,  

Functional Outcomes(tgid=23)

hepatoP↑, 1,   RenoP↑, 1,   toxicity↓, 1,  

Infection & Microbiome(tgid=24)

Bacteria↓, 1,  
Total Targets: 10

Scientific Paper Hit Count for: Ca+2, Calcium Ion Ca+2
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells
Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:263  Target#:38  State#:%  Dir#:%
wNotes=0 sortOrder:rid,rpid

 

Home Page