Role of altholactone in inducing type II apoptosis signalling pathway and expression of cancer‐related genes in cervical carcinoma HeLa cell line

Abstract

Goniothalamus species (Annonaceae) is a shrub that grows in the rainforest of tropical Asia. Several compounds have been isolated and exhibit the potential use for cancer treatment. In this work, altholactone isolated from Goniothalamus macrophyllus was investigated for its cytotoxicity, apoptosis signalling and the expression of cancer‐related genes in the cervical carcinoma HeLa cells. Cytotoxicity was evaluated by MTT assay. Apoptotic characteristics were evaluated by morphological studies. Caspase‐3 activity was detected using a fluorogenic substrate. Cytochrome c release from mitochondria and protein Bid were determined by Western blotting and cancer‐related genes expression by RT‐PCR. The results demonstrated that altholactone was cytotoxic to HeLa (IC50 = 9.6 μg/mL), and apoptotic cell death was manifested by appearance of chromatin condensation and caspase‐3 activation, which was inhibited by specific inhibitors of both caspase‐8 and ‐9. Release into the cytosol of cytochrome and cleavage of Bid occurred. Altholactone also caused a decrease in bcl‐2 and an increase in p53 expression. These unique properties of altholactone suggest a potential for cancer chemotherapy.

Altholactone induces reactive oxygen species-mediated apoptosis in bladder cancer T24 cells through mitochondrial dysfunction, MAPK-p38 activation and Akt suppression

“…2). These results demonstrated that altholactone induced growth inhibition of T24 cells similar to the effects on other types of cancer cells including leukemia (10), colorectal (11) and cervical cancer cells (8).…”

“…1) or goniothalenol belongs to the styryllactone family and is a tetrahydrofurano-2-pyrone. It has been reported to exhibit antitumor activity, including inhibition of Bcl-2 and increased p53 expression in human cervical cancer HeLa cells (8), suppression of cell growth of human lung cancer COR-L23 cells (9), and induction of apoptosis in human HL-60 leukemia cells through oxidative stress (10) and in human colorectal cancer (CRC) cells through caspasedependent and -independent apoptotic pathways (11).…”

Altholactone Inhibits NF-κB and STAT3 Activation and Induces Reactive Oxygen Species-Mediated Apoptosis in Prostate Cancer DU145 Cells

“…The results showed that 5 mM NAC diminished the effect of alhtolactone on DU145 cells and support the notion that alhtolactone induces cytotoxic effects by targeting the ROS metabolism (data not shown). These findings are the parallel with the previous studies in which alhtolactone has been reported as a growth inhibitor of different cancer cell lines such as bladder cancer T24 cells [ 15 ], cervical carcinoma HeLa cells [ 13 ] and human colorectal cancer cells [ 12 ].…”

“…Zhao and Li [ 15 ] have reported that altholactone exerts its in vitro anticancer action by Akt inhibition. Hence, considering current and previous findings, there is the possibility that altholactone may also act via inhibition of the PI3K-Akt-mTOR pathway that plays a key role in oncogenesis [ 39 , 40 ] and with possibility that altholactone promoted p53 expression, as previously has been reported [ 13 , 41 ], could mediate altholactone-induced anticancer action. Further in vivo or preclinical studies are needed to elucidate the anticancer potential of altholactone in combination or adjuvant therapies for the treatment of cancers.…”

“…Altholactone is one of such agents that can inhibit cancer progression. Altholactone ( Figure 1 A), a natural tetrahydrofurano-2-pyrone, isolated from Goniothalamus spp., which belongs to the styryl-lactone family, has been reported to display anticancer activities in human colorectal cancer (HCRC) cells through caspases-dependent and independent apoptotic pathways [ 12 ], in the cervical carcinoma HeLa cell line by decreasing Bcl-2 and increasing p53 expression [ 13 ] and in leukemia HL-60 cells by induction of apoptosis via oxidative stress [ 14 ]. We previously reported that altholactone inhibited cell growth and induced apoptosis in human bladder cancer T24 cells by causing mitochondrial membrane potential imbalance followed by MAPK-p38 activation and suppression of the Akt pathway [ 15 ].…”