Kalanchoe pinnata (Lam.) Pers. Leaf ethanolic extract exerts selective anticancer activity through ROS-induced apoptotic cell death in human cancer cell lines.
The leaves of Kalanchoe pinnata (Lam.) Pers. (K. pinnata), a succulent plant native to tropical regions, are used as a medicinal alternative against cancer in several countries worldwide; however, its therapeutic potential to fight cancer has been little addressed. In this study, we analyzed the phytochemical content, antioxidant capacity, and selectivity of K. pinnata leaf ethanolic extract against different human cancer cell lines in vitro.
This study subjected the ethanolic extract to enzymatic assays to quantify the phytochemical content (phenolics, flavonoids, and anthraquinones) and its radical scavenging and iron-reducing capacities. Also, the phytoconstituents and major phenolic compounds present in the extract's subfractions were identified by GC-MS, HPLC, and NMR. Human cancer (MCF-7, PC-3, HT-29) and normal colon (CoN) cell lines were treated with different concentrations of K. pinnata leaf ethanolic extract, and the changes in cell proliferation (sulforhodamine B assay), caspases activity (FITC-VAD-FMK reporter), mitochondrial membrane potential (MMP, rhodamine 123 assay), chromatin condensation/fragmentation (Hoechst 33342 stain), and ROS generation (DCFH2 probe assay) were assessed.
The results showed that the K. pinnata leaf ethanolic extract is rich in phytoconstituents with therapeutic potential, including phenols (quercetin and kaempferol), flavonoids, fatty acid esters (34.6% of the total composition), 1- triacontanol and sterols (ergosterol and stigmasterol, 15.4% of the total composition); however, it presents a poor content of antioxidant molecules (IC50 = 27.6 mg/mL for H2O2 scavenging activity vs. 2.86 mg/mL in the case of Trolox). Notably, the extract inhibited cell proliferation and reduced MMP in all human cell lines tested but showed selectivity for HT-29 colon cancer cells compared to CoN normal cells (SI = 8.4). Furthermore, ROS generation, caspase activity, and chromatin condensation/fragmentation were augmented significantly in cancer-derived cell lines, indicating a selective cytotoxic effect.
These findings reveal that the K. pinnata leaf ethanolic extract contains several bioactive molecules with therapeutic potential, capable of displaying selective cytotoxicity in different human cancer cell lines.
Faundes-Gandolfo N
，Jara-Gutiérrez C
，Párraga M
，Montenegro I
，Vera W
，Escobar M
，Madrid A
，Valenzuela-Valderrama M
，Villena J
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《BMC Complementary Medicine and Therapies》
Antitumor action of curcumin in human papillomavirus associated cells involves downregulation of viral oncogenes, prevention of NFkB and AP-1 translocation, and modulation of apoptosis.
Curcumin (diferuloyl methane), the major yellow pigment from the rhizomes of turmeric (Curcuma longa Linn), has anticancer properties. Infection with high-risk human papillomaviruses (HPV) leads to development of cervical carcinoma, predominantly through the action of viral oncoproteins E6 and E7. The present study aims at analyzing the antitumor and antiviral properties of curcumin, on HPV associated cervical cancer cells. Our findings indicate curcumin to be cytotoxic to cervical cancer cells in a concentration-dependent and time-dependent manner. The cytotoxic activity was selectively more in HPV16 and HPV18 infected cells compared to non-HPV infected cells. Balance between tumor cell proliferation and spontaneous cell death via apoptosis had an important role in regulation of tumor cell growth. Curcumin-induced apoptosis in cervical cancer cells. Morphological hallmarks of apoptosis such as nuclear fragmentation and internucleosomal fragmentation of DNA were observed. Curcumin also selectively inhibited expression of viral oncogenes E6 and E7, evident from RT-PCR and Western blotting data. Electrophoretic mobility shift assay revealed that activation of NFkappaB-induced by TNFalpha is down regulated by curcumin. Curcumin blocked IkBalpha phosphorylation and degradation, leading to abrogation of NFkappaB activation. Curcumin also down regulated the expression of COX-2, a gene regulated by NFkappaB. Binding of AP-1, an indispensable component for efficient epithelial tissue-specific gene expression of HPV was also selectively down regulated by curcumin. These results provide attractive data for the possible use of curcumin in the management of HPV associated tumors.
Divya CS
，Pillai MR
《MOLECULAR CARCINOGENESIS》
A novel polysaccharide, isolated from Angelica sinensis (Oliv.) Diels induces the apoptosis of cervical cancer HeLa cells through an intrinsic apoptotic pathway.
A novel polysaccharide isolated from Angelica sinensis, named APS-1d showed cytotoxic activity towards several cancer cell lines in vitro. However, the precise antitumor mechanisms of this compound are unknown. In this study, we investigated the pro-apoptotic effects of APS-1d in human cervical cancer HeLa cells both in vitro and in vivo, and further elucidated the mechanisms of this action. Inhibition of HeLa cell proliferation was determined by MTT assay and the therapeutic efficacy of APS-1d was evaluated by human cancer xenografts in nude mice. Cell apoptosis was examined with flow cytometry and TUNEL assay. The mechanism of action of APS-1d was investigated by Western blot analysis. APS-1d decreased HeLa cell proliferation in a concentration- and time-dependent manner in vitro. In addition, APS-1d significantly inhibited tumor growth in athymic nude mice. Characteristic manifestations of apoptosis including apoptotic morphological features and the sub- G(0)/G(1) peaks were observed when the cells were treated with APS-1d. Further analysis showed that APS-1d-induced apoptosis was associated with the regulation of Bcl-2 family protein expression, a decrease in the mitochondrial membrane potential, and an increase in the cytosolic cytochrome c levels. Sequentially, APS-1d increased the activities of caspase-9, -3, and poly (ADP-ribose) polymerase in a concentration-dependent manner, however, no obvious activation of Bid and caspase-8 was observed. Pretreatment with Z-LEHD-FMK, a specific inhibitor of caspase-9, significantly attenuated APS-1d-induced cell apoptosis, and activation of caspase-3. Taken together, our studies indicate that APS-1d is capable of inhibiting HeLa cell proliferation and inducing apoptosis in these cells which primarily involves the activation of the intrinsic mitochondrial pathway.
Cao W
，Li XQ
，Wang X
，Fan HT
，Zhang XN
，Hou Y
，Liu SB
，Mei QB
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ResearchGate
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