Shikonin promotes adriamycin-induced apoptosis by upregulating caspase-3 and caspase-8 in osteosarcoma

Abstract

Osteosarcoma is the most common primary malignant bone tumor. Cancer cells employ a host of mechanisms to develop resistance to adriamycin (ADM) or other chemotherapeutic drugs. Shikonin (SK), an active constituent extracted from a Chinese medicinal herb, has been shown to cooperate with ADM in the treatment of osteosarcoma and certain other types of cancer by contributing to the response rate of chemotherapy and the side effects. The aim of the present study was to investigate the role and underlying mechanism of SK in chemotherapy for osteosarcoma. In the present study, a CCK-8 assay was performed to assess cell survival rate in vitro. Western blot analysis was performed to determine the expression levels of B-cell lymphoma 2-associated X protein (Bax), caspase-3, caspase-8, and poly (ADP-ribose) polymerase (PARP). Flow cytometry was used to analyze cell cycle and cell death. The survival rate of cells decreased significantly in a dose- and time-dependent manner when treated with a combination of SK and ADM. Western blot analysis revealed increased expression levels of Bax, caspase-3, caspase-8 and PARP in U2OS and MG63 cells 48 h following treatment with SK and ADM. Flow cytometric analysis showed that the combined treatment of SK and ADM significantly induced apoptosis in the osteosarcoma cells. Taken together SK cooperated with ADM to promote apoptosis, possibly by inducing caspase-3- and caspase-8-dependent apoptosis. SK may be a potential enhancer in the treatment of drug-resistant primary osteosarcoma.

The Critical Role of PTEN/PI3K/AKT Signaling Pathway in Shikonin-Induced Apoptosis and Proliferation Inhibition of Chronic Myeloid Leukemia

“…As a major component of Zicao, shikonin exhibits anti-tumor activity [4,19] and has been reported to be less cytotoxic [20][21][22][23] and circumvent drug resistance [24] of various tumor cell lines. In the present study, we tested the effects of shikonin on K562 cells.…”

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

“…Besides, shikonin can also potentiate the anti-cancer effects of gemcitabine through NF-kB suppression and by regulating RIP1 and RIP3 expressions in human pancreatic cancer [632,633]. Shikonin is also reported to promote the efficacy of adriamycin in lung cancer and osteosarcoma [634,635], and enhance sensitization to cisplatin in colorectal cancer [636]. Apart from the synergistic effect of shikonin, the combination of shikonin and paclitaxel reverses MDR in human ovarian cancer A2780 cells [10].…”

Herbal Remedy for Osteosarcoma - Challenging Evolution

“…Shikonin (SK), an active constituent extracted from a Chinese medicinal herb, Lithospermum erythrorhizon, has been shown to exert antitumor effects. Western blot analysis revealed increased expression levels of Bax, caspase-3, caspase-8, and PARP in U2OS and MG63 cells with the treatment of SK and ADM. Flow cytometric analysis showed that the combined treatment of SK and ADM significantly precipitated apoptosis probably by inducing caspase-3 and caspase-8 dependent apoptosis in the OS cells and maybe ability enhancer in the treatment of drugresistant primary OS [40].…”