**1. Introduction**

Cancer is a major global health challenge that affects millions of people annually across the world. Recent estimates showed about 18.1 million new cases of cancer and 9.6 million cancer-related deaths worldwide [1]. Moreover, due to population growth, aging, and increased prevalence of key risk factors, this figure is expected to rise in the coming years. According to the same report, different from other parts of the world, cancer death (7.3%) is higher than cancer incidence (5.2%) in Africa. This is mainly attributed to lack of adequate health care facilities as well as professionals, lack of early cancer detection system, and poor access to chemotherapeutic treatments. Due to these and other

factors, including socio-economic conditions, the majority of the population of Africa has relied on traditionally used medicinal herbs and/or plants as a monotherapy or in combination with clinically approved anticancer drugs.

Medicinal plants have been a rich source of clinically effective anticancer agents for the past few decades. Over 60% of the currently used anticancer drugs are either directly derived from plants or inspired by their novel phytochemicals [2] and/or unique ligands as secondary metabolites. In spite of such success, the importance of medicinal plants as a source of leads for anticancer drug discovery was marginalized in comparison with other advanced approaches. This could be due to issues associated with intellectual property rights and securing not enough amounts of plant material which results in the slowness of working with natural products [3]. However, despite these drawbacks, medicinal plant-based drug discovery and development has made a comeback to find potent and affordable natural products with a new mechanism of action and better toxicological profile due to structural diversity of natural product small molecules (NPSM). For instance, among small molecules approved for cancer treatment between 1940 and 2014, 49% are derived and/or originated from natural products [4].

Ethiopia inherited a unique array of fascinating flora from its diverse landscape. Due to the geographical location and diversity, which favors the existence of different habitat and vegetation zones, Ethiopia is home to a variety of plant species. The Ethiopian flora is estimated to contain 6027 species of higher plants of which more than 10% are estimated to be endemic [5]. Different authors have compiled ethnobotanical and ethnopharmacological profiles and reviews of Ethiopian traditionally used medicinal plants [6,7]. However, published reports regarding isolated bioactive compounds of traditionally used Ethiopean medicinal plants, especially those with cytotoxic properties are scant. However, investigations conducted on plants with cytotoxic properties out side Ethiopia, include the study on *Catha edulis* Forsk [8,9], *Artemisia annua* L., *Rumex abyssinicus* Jacq. [9]., *Carissa spinarum* L., *Dodonaea angustifolia* L.f., *Jasminum abyssinicum* Hochst. ex DC., *Rumex nepalensis* Spreng., *Rubus steudneri* Schweinf. and *Verbascum sinaiticum* Benth. [10], *Viola abyssinica* Steud. ex Oliv. [11], *Xanthium strumarium* L. [12], *Senna singueana* (Del). Lock [13], *Glinus lotoides* L. [14], *Kniphofia foliosa* Hochst [15], *Sideroxylon oxyacanthum* Baill., *Clematis simensis* Fresen, and *Dovyalis abyssinica* (A. Rich) Warburg [16]. Thus, for further evaluation, identification, or modification of anticancer leads, thorough review of the chemistry and pharmacology of medicinal plants from relatively uncovered traditional medical systems is crucial. Therefore, in continuation of our previous mini-review [17], in which we documented both ethnobotanical and ethnopharmacological evidence of Ethiopian anticancer plants involving mostly the cytotoxic and antioxidant activities of crude extracts, here, in this review, we comprehensively document the cytotoxic and antiproliferative constituents from anticancer plants those traditionally used in Ethiopia. The secondary metabolites reported from each medicinal plant species are categorized based on the class of natural products they belong to.
