Effect of DMSO and DFMO on rat prostate tumor growth

Abstract

An anaplastic, metastatic subline of the Dunning rat tumor was exposed to non-cytodestructive doses of the cellular differentiation agents dimethylsulfoxide and difluoromethylornithine. Copenhagen rats hosting prostate tumors were evaluated by comparing solid tumor growth resulting from injection of treated cells with solid tumor growth of untreated control cells. Results showed significantly slower solid tumor growth after a 15 day in vitro exposure of cells to either agent, after oral treatment of host animals for 20 days with either agent before injection of untreated tumor cells, and after oral treatment of host animals with either agent initiated on the day of untreated tumor cell injection. Treatment of animals with established tumors with either agent also had an inhibitory effect on tumor growth, and the effect was related to the length of treatment. Thus, exposure of these highly malignant rat prostate carcinoma cells to non-cytotoxic doses of either agent induced slower tumor growth rates. Treatment with either agent could have selected for a slower growing population of tumor cells. Since a slowing of cell cycle transit times is an early indicator of cellular differentiation, these results could reflect an increase in the capacity of the malignant cells to differentiate.

Butyrate analogue, isobutyramide, inhibits tumor growth and time to androgen‐independent progression in the human prostate LNCaP tumor model

“…The rationale for differentiation therapy in prostate cancer is supported by several lines of evidence. First, prostatic cancer growth and differentiation can be altered by various differentiating agents, including retinoids [Slawin et al, 1991;Pollard et al, 1991;Dahiya et al, 1995], dimethylsulfoxide (DMSO) [Carvalho et al, 1989;Kaneski et al, 1991], butyrate [Figg et al, 1994], and phenylacetate [Samid et al, 1993]. For example, noncytotoxic doses of DMSO reduce Dunning rat prostate cancer cell growth rates [Carvalho et al, 1989;Kaneski et al, 1991], while fenretinide inhibits carcinogenesis and metastases in Lobund-Wistar rats [Pollard et al, 1991] as well as tumor incidence and growth of rasϩmyc-induced carcinomas in the mouse prostate reconstitution model [Slawin et al, 1991].…”

“…First, prostatic cancer growth and differentiation can be altered by various differentiating agents, including retinoids [Slawin et al, 1991;Pollard et al, 1991;Dahiya et al, 1995], dimethylsulfoxide (DMSO) [Carvalho et al, 1989;Kaneski et al, 1991], butyrate [Figg et al, 1994], and phenylacetate [Samid et al, 1993]. For example, noncytotoxic doses of DMSO reduce Dunning rat prostate cancer cell growth rates [Carvalho et al, 1989;Kaneski et al, 1991], while fenretinide inhibits carcinogenesis and metastases in Lobund-Wistar rats [Pollard et al, 1991] as well as tumor incidence and growth of rasϩmyc-induced carcinomas in the mouse prostate reconstitution model [Slawin et al, 1991]. Second, when androgens are used as differentiation agents and replaced intermittently after castration, repeated cycles of androgen-induced differentiation and androgen withdrawal-induced PSA nadirs are possible, and the time to androgen independence is delayed [Akakura et al, 1993;Sato et al, 1996].…”

Efficacy of EZH2 inhibitory drugs in human papillomavirus-positive and human papillomavirus-negative oropharyngeal squamous cell carcinomas

“…Historically, DMSO has been shown to have multiple effects on cellular functioning [ 55 ]. Its most noteworthy trait includes its ability to induce differentiation in malignant tumor cells at low doses, resulting in a loss of tumorigenicity and altered cell morphology into more mature, differentiated cells in leukemias, colon, prostate, lung, and breast carcinomas [ 56 – 58 ]. The exact mechanism of DMSO’s ability to induce differentiation remains relatively unknown; however, a study performed by Iwatani et al suggests DMSO impacting a cell’s epigenetic profile.…”

Cryopreservation: A Comprehensive Overview, Challenges, and Future Perspectives

“…employed a cultured medium for freezing isolated MSCs from rat's bone marrow, in addition to a 10% fetal calf serum and a 5% DMSO. [ 138 ] Other researchers have employed a similar solution composition to cryopreserve human MSCs isolated from the bone marrow. Pal et al.…”