Combination Effects of Salvianolic Acid B with Low-Dose Celecoxib on Inhibition of Head and Neck Squamous Cell Carcinoma Growth In vitro and In vivo

Abstract

Head and neck squamous cell carcinoma (HNSCC) development is closely associated with inflammation. Cyclooxygenase-2 (COX-2) is an important mediator of inflammation. Therefore, celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib, but it seems likely that this may be diminished by lowering its dose. We found that salvianolic acid B (Sal-B), isolated from Salvia miltiorrhiza Bge, can effectively suppress COX-2 expression and induce apoptosis in a variety of cancer cell lines. In this study, we report that combination of Sal-B with low-dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. The combination effects were assessed in four HNSCC cell lines (JHU-06, JHU-011, JHU-013, and JHU-022) by evaluating cell viability, proliferation, and tumor xenograft growth. Cell viability and proliferation were significantly inhibited by both the combined and single-agent treatments. However, the combination treatment significantly enhanced anticancer efficacy in JHU-013 and JHU-022 cell lines compared with the single treatment regimens. A half-dose of daily Sal-B (40 mg/kg/d) and celecoxib (2.5 mg/kg/d) significantly inhibited JHU-013 xenograft growth relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was associated with profound inhibition of COX-2 and enhanced induction of apoptosis. Taken together, these results strongly suggest that combination of Sal-B, a multifunctional anticancer agent, with low-dose celecoxib holds potential as a new preventive strategy in targeting inflammatory-associated tumor development. Cancer Prev Res; 3(6); 787-96. ©2010 AACR.

Celecoxib Enhances Radiosensitivity via Induction of G₂-M Phase Arrest and Apoptosis in Nasopharyngeal Carcinoma

“…NSAIDs could suppress COX-2 expression and prevent the effects of prostaglandins. Celecoxib, the first selective COX-2 inhibitor approved by the U.S. Food and Drug Administration, has been reported to prevent carcinogenesis in both animals and humans [11,12,13]. Moreover, it has been reported that the chemotherapy, including celecoxib when used at low dose, may be able to enhance the efficacy of radiation treatment on the cancer cells [14,15,16].…”

Evaluation of antigenotoxic potential of salvianolic acid B with hydrogen peroxide on human peripheral blood leukocytes in vitro

“…Utvrđeno je da Sal B dostiže maksimum koncentracija u plazmi već 0,5-1 sat nakon oralne primene i njeni metaboliti mogu biti prisutni u organizmu i nakon 180 minuta od trenutka primene (17). U dosadašnjim studijama glavni zabeleženi efekti Sal B jesu kardioprotektivna, neuroprotektivna i antitumorska svojstva, zasnovana pre svega na njenom antioksidativnom potencijalu (17,18,32,33,34). Pokazano je da Sal B štiti ćelije endotela, arterijske glatke mišićne ćelije i kardiomiocite od slobodnih radikala i peroksidacije, tako što redukuje intracelularni oksidativni stres (17).…”

“…Salvianolična kiselina B ima jako hemopreventivno dejstvo koje ostvaruje najverovatnije pomoću antioksidativnih i antiinflamatornih mehanizama. Naime, pretpostavlja se da je modulacija apoptoze preko vodonik-peroksida jedan od glavnih puteva za suzbijanje rasta ćelija kancera (32,34). Do sada nisu zabeleženi efekti Sal B na integritet jedarne DNK pomoću alkalnog Komet testa i ova studija je po prvi put prikazala odsustvo genotoksičnosti i antigenotoksični potencijal Sal B.…”

Salvianolic acid B protects against myocardial damage caused by nanocarrier TiO₂; and synergistic anti-breast carcinoma effect with curcumin via codelivery system of folic acid-targeted and polyethylene glycol-modified TiO₂ nanoparticles

“…11 Apart from anti-inflammation, anticoagulation, and antioxidation, Sal B has also shown obvious anticancer activity in a variety of cancer cell lines, including prostate, breast, liver, and head and neck squamous cell cancers. [12][13][14] Curcumin (Cur) is diferuloylmethane or 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-hepadiene-3,5-dione, and has presented a comprehensive array of pharmacological properties, such as anti-inflammatory, antioxidant, anticancer, antimicrobial, antiparasitic, antitumor, antiangiogenic, and antimutagenic effects. 15 Currently, Cur is used mainly for inhibiting cancer in a variety of cell lines, and has expressed obvious antitumor effects, eg, in breast cancer and ovarian cancer.…”