Tegillarca granosa extract Haishengsu inhibits tumor activity via a mitochondrial‑mediated apoptotic pathway

Abstract

Haishengsu (HSS) is an active natural extract isolated from Tegillarca granosa, which has previously been demonstrated to inhibit the proliferation of several types of cancer cells in vitro. Our previous study indicated that HSS may induce apoptosis to suppress growth of human hepatocellular carcinoma BEL‑7402 cells by activating Fas pathway. The present study demonstrated that HSS treatment induces the in vitro apoptosis of BEL‑7402 cells via the mitochondrial‑mediated apoptotic pathway detected by DNA fragmentation assay, caspase activity assay and transmission electron microscopy assay, and inhibits tumor xenograft growth in vivo. Alterations in apoptotic regulatory proteins were detected, including decreased expression of B‑cell lymphoma2 (Bcl‑2), upregulation of Bcl‑2‑associated X protein and mitochondrial cytochrome c release, and downstream activation of apoptotic signaling. Furthermore, apoptotic induction was caspase‑dependent, as indicated by cleavage of the caspase substrate, poly (ADP‑ribose) polymerase. Oral administration of 62.5‑250 mg/kg HSS markedly educed the growth of hepatocellular carcinoma tumor xenografts in nude mice. In addition, immunohistochemical staining for caspase‑3 protein and transmission electron microscopy further indicated the induction of apoptosis in these tumor tissues. Taken together, the present study demonstrated that HSS may effectively induce apoptosis to suppress the growth of BEL‑7402 cells in vitro and in vivo, and therefore may hold promise for further development as a novel cancer therapy.